Two factor reprogramming of human neural stem cells into pluripotency.
Two factor reprogramming of human neural stem cells into pluripotency.
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DOI：
10.1371/journal.pone.0007044
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发表时间：
2009-09-18
期刊：
影响因子：
3.7
通讯作者：
Kaspar BK
中科院分区：
文献类型：
--
作者：
Hester ME;Song S;Miranda CJ;Eagle A;Schwartz PH;Kaspar BK
将人类体细胞重新编程为多能性是开发基于体外的人类疾病模型的宝贵资源，并且具有获得患者特异性多能性干细胞的巨大潜力。最近，小鼠神经干细胞（NSCs）已被证明能够通过强迫表达Oct3/4和Klf4而重编程为多能状态；然而，尚不清楚这种相同的策略是否适用于人类NSCs，这将导致更相关的多能干细胞用于模拟人类疾病。在这里，我们证明OCT3/4和KLF4确实足以在两周的时间内诱导人类NSCs的多能性，并且在分子上与人类胚胎干细胞没有区别。此外，人类nsc衍生的多能干细胞在体外和体内都可以分化为所有三种生殖谱系。我们认为，人类NSCs是产生人类iPS细胞的一个有吸引力的细胞来源，因为它们只需要两个因子就可以诱导成多能性，从而消除了对c-MYC的需要。因此，体外人类疾病模型可以由来自人类NSCs的iPS细胞生成。
Reprogramming human somatic cells to pluripotency represents a valuable resource for the development of in vitro based models for human disease and holds tremendous potential for deriving patient-specific pluripotent stem cells. Recently, mouse neural stem cells (NSCs) have been shown capable of reprogramming into a pluripotent state by forced expression of Oct3/4 and Klf4; however it has been unknown whether this same strategy could apply to human NSCs, which would result in more relevant pluripotent stem cells for modeling human disease. Here, we show that OCT3/4 and KLF4 are indeed sufficient to induce pluripotency from human NSCs within a two week time frame and are molecularly indistinguishable from human ES cells. Furthermore, human NSC-derived pluripotent stem cells can differentiate into all three germ lineages both in vitro and in vivo. We propose that human NSCs represent an attractive source of cells for producing human iPS cells since they only require two factors, obviating the need for c-MYC, for induction into pluripotency. Thus, in vitro human disease models could be generated from iPS cells derived from human NSCs.
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